Immune checkpoint molecules. Possible future therapeutic implications in autoimmune diseases.

During host immune response, an initial and sufficient activation is required to avoid infection and cancer, yet an excessive activation bears the risk of autoimmune reactivity and disease development. This fastidious balance of the immune system is regulated by co-stimulatory and co-inhibitory molecules, also known as immune checkpoints. Both excessive co-stimulation and insufficient co-inhibition can induce the activation and proliferation of autoreactive cells that may lead to the development of autoimmune diseases. During the last decade, a growing number of new immune checkpoint receptors and ligands have been discovered, providing an attractive approach to investigate their implication in the pathogenesis of autoimmune diseases and their potential role as targets for effective therapeutic interventions. In this review, we focus on the roles and underlying mechanisms of co-stimulatory and co-inhibitory receptors and other molecules that function as immune checkpoints in autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome, type I diabetes and inflammatory bowel disease. We also summarize previous and current clinical trials targeting these checkpoint pathways in autoimmune diseases and discuss further therapeutic implications and possible risks and challenges.

Forecast model analysis for the morbidity of tuberculosis in Xinjiang, China.

Tuberculosis is a major global public health problem, which also affects economic and social development. China has the second largest burden of tuberculosis in the world. The tuberculosis morbidity in Xinjiang is much higher than the national situation; therefore, there is an urgent need for monitoring and predicting tuberculosis morbidity so as to make the control of tuberculosis more effective. Recently, the Box-Jenkins approach, specifically the autoregressive integrated moving average (ARIMA) model, is typically applied to predict the morbidity of infectious diseases; it can take into account changing trends, periodic changes, and random disturbances in time series. Autoregressive conditional heteroscedasticity (ARCH) models are the prevalent tools used to deal with time series heteroscedasticity. In this study, based on the data of the tuberculosis morbidity from January 2004 to June 2014 in Xinjiang, we establish the single ARIMA (1, 1, 2) (1, 1, 1)12 model and the combined ARIMA (1, 1, 2) (1, 1, 1)12-ARCH (1) model, which can be used to predict the tuberculosis morbidity successfully in Xinjiang. Comparative analyses show that the combined model is more effective. To the best of our knowledge, this is the first study to establish the ARIMA model and ARIMA-ARCH model for prediction and monitoring the monthly morbidity of tuberculosis in Xinjiang. Based on the results of this study, the ARIMA (1, 1, 2) (1, 1, 1)12-ARCH (1) model is suggested to give tuberculosis surveillance by providing estimates on tuberculosis morbidity trends in Xinjiang, China.

Biomarkers for the evaluation of population health status 16 years after the intervention of arsenic-contaminated groundwater in Xinjiang, China.

The arsenicosis endemic area in the region of Kuitun and Chepaizi, Dzungaria district, Xinjiang, People Republic of China was the first identified arsenic endemic area in China where arsenic concentration of up to 850 µg/L in the groundwater was reported. An intervention was put in place in 1985 by government to provide an alternative water source at a centralized community level. Sixteen years on since the intervention, we evaluated the health status of 178 villagers from endemic and 179 villagers from control sites. Biomarkers in their urine, included arsenic, porphyrins and malondialdehyde (MDA) were measured and the prevalence of skin lesions was also assessed. The average urinary arsenic (117 ± 8.3 µg/g of creatinine) from the endemic-villages was significantly higher (p<0.001) than that of the controls (73.6 ± 3.2 µg/g of creatinine) while no significant difference was found in urinary porphyrins and malondialdehyde concentrations in the overall studies subjects from these two areas. However when the urinary arsenic was higher than 150 µg/g of creatinine, MDA and porphyrins were higher in the endemic-villagers compared to the controls. Fifty-one out of 178 people from the arsenic endemic area showed skin lesions related to arsenicosis but these were absent among villagers from the control site. Of particular concern, skin lesions related to arsenicosis were observed in 4 out of 9 subjects 16 years of age or younger who were from different villages and born after the completion of water intervention. Although sporadic exposure and/or voluntary drinking contaminated water were thought to be a contributor of arsenicosis after the water intervention, the contribution from other dietary arsenic intakes remain unclear.

[Distribution of hepatitis B virus genotypes and subgenotypes among chronically infected patients in Xinjiang Uighur.].

OBJECTIVE: To investigate the distribution of Hepatitis B virus genotypes and subgenotypes among patients with chronic hepatitis B in Xinjiang Uighur. METHODS: The HBV genotypes and subgenotypes were analyzed by PCR-restriction fragment length polymorphism in 109 patients with chronic hepatitis B. RESULTS: Two HBV genotypes, genotype C (45.9%) and genotype C/D (29.4%) were prevalent, genotype B (8.3%) and genotype D (16.5%) were also found in Xinjiang Uighur. Genotype C had two subgenotypes, C1 (54%) and C2 (46%). Genotype B had only one subgenotype, i.e. Ba. The subgenotype C2 was associated with cirrhosis and hepatocellular carcinoma. CONCLUSION: In Uygurs, the most common HBV genotypes were C and C/D, and the subgenotype C2 was associated with cirrhosis and hepatocellular carcinoma.

[Study on the body mass index reference norm for defining overweight and obesity in school-age children and adolecents with Uygur and Han ethnic backgrounds in Urumqi].

OBJECTIVE: To construct and compare the body mass index (BMI) cutoff points for defining overweight and obesity in school-age children and youths with Uygur and Han ethnic backgrounds in Xinjiang, China. METHODS: A total number of 9146 boys and girls in Urumqi, Xinjiang, aged 7-18 years, were recruited by stratifying and clustering sampling from April to June 2004. Demographic and anthropometric data, including body weight and standing height, were collected. Questionnaires and standard methods were used and BMI was calculated by weight/height2. BMI centile curves with age were drawn according to gender and ethnicity, using LMS software (Tim cole and Huiqi Pan) which were making the centile curves passing through 25 kg/m2 and 30 kg/m2, and 24 kg/m2 and 28 kg/m2 at age of 18 for overweight and obesity respectively. RESULTS: The age and sex specific BMI centile curves were drawn for children with Uygur and Han ethnicities. Data showed that BMI increased with age. The centile of BMI curves, P94.46 and P99.58 for Uygur boys, P92.44 and P99.64 for Uygur girls, P85.05 and P97.26 for Han boys, P90.92 and P99.03 for Han girls, which passing through 25 kg/m2 and 30 kg/m2 by IOTF recommendation at age 18, were constructed. Under the basis of WGOC recommendation, the points that passing through 24 kg/m2 and 28 kg/m2 at age 18 were P90.54 and P98.86 for uygur boys, P86.96 and P98.77 for uygur girls, P78.98 and P94.72 for Han boys, P86.15 and P97.56 for Han girls. The BMI cutoff points for defining overweight and obesity were suggested. CONCLUSION: To the best of our knowledge, the present study established the BMI cutoff points for Uygur ethnic school-aged children and youths for identifying overweight and obesity. There was ethnic difference in the BMI distribution with age. We recommended using the BMI cutoff points proposed by the current study to identify those overweight and obese children in Urumqi.

Ethnic differences in body mass index and prevalence of obesity in school children of Urumqi City, Xinjiang, China.

OBJECTIVE: To investigate the prevalence of obesity and distribution of body mass index (BMI) in school children of four ethnic groups in Urumqi, Xinjiang, China. METHODS: A total of 55508 school children of Han, Hui, Uygur and Kazak nationalities aged 8-18 years were selected by a cluster sampling from a districts of Urumqi City for anthropometric measurement and demographic survey. Prevalence of obesity and overweight and distribution of body mass index (BMI) by gender, age, and nationality were analyzed and compared. Cutoff points of BMI for defining obesity and overweight were based on the proposal set by the Working Group on Obesity in China (WGOC) to assess age-, gender- and nationality-specific prevalence of obesity and overweight. RESULTS: Prevalence of obesity was 5.34%, 6.78%, 3.39 %, and 1.22% for boys and 2.61%, 1.83%, 1.78%, and 1.40% for girls of Han, Hui, Uygur and Kazak nationalities, respectively. Prevalence of obesity tended to decrease with age overall, whereas that of overweight increased with age in Han children. CONCLUSIONS: Prevalence of obesity in school children in Urumqi varies with their nationalities and is lower than that of an average national level and a level of western countries. Obesity is more prevalent in boys than in girls of Urmuqi overall, which is just the opposite in Kazak children. Han boys and Hui girls have the highest prevalence of obesity and Kazak boys and girls have the lowest ones. Prevalence of obesity decreases with age, but that of overweight shows a different trend.

[Detection of HPV16 E6 gene in cervical tissues by quantitative polymerase chain reaction].

OBJECTIVE: To establish a method for detection of Human Papillomavirus (HPV) type16 E6 gene in Cervical carcinomas Specimens. To study the relationship between the quantities of HPV16 E6 (Human papillomavirus type16 E6 gene) in cervical tissues and the course of cervical disease in Xinjiang. METHODS: HPV16E6 gene and beta-actin was detected in parallel by FQ-PCR (fluorescence quantitative PCR). The number of copies of HPV16 E6 gene and beta-actin was detected in parallel by FQ-PCR (fluorescence quantitative PCR) in tissues of 69 cervical cancer, 65 cervical intraepithelial neoplasia (CIN), 33chronic cervicitis and samples of 96 cervical smear samples of vaginitis and cervicitis. The variation in HPV copies per genomic DNA equivalent can be estimated by dividing the HPV copy number by the beta-actin copy number. RESULTS: The positive rate of HPV16 E6 gene was 83.0%, 75.7%, 93.3% and 3.3% in tissues of cervical cancer, cervical intraepithelial neoplasia (CIN), chronic cervicitis and samples of cervical smear respectively. The amount of HPV16 E6 gene was gradually higher by the developing of the course of cervical disease. They have positive rank correlation, r = 0.83, P < 0.01. CONCLUSION: The study underscores the importance of the relationship between the HPV16 E6 gene and the course of cervical disease in Xinjiang. It also suggests that the quantification of HPV16 E6 gene may be useful as a prognostic tool to identify women who are at increased risk of developing cervical cancer. This method may be applied to studies of a number of issues related to the natural history of cervical cancer, such as the amounts of HPV in high- and low-grade lesions.